rs113716376

chr15-77614077-G-A

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_Strong BP6_Moderate BP7 BS1 BS2

The NM_032808.7(LINGO1):c.1830C>T(p.Asp610=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00161 in 1,610,260 control chromosomes in the GnomAD database, including 38 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0080 (18 hom., cov: 33)
  • Exomes 𝑓: 0.00094 (20 hom.)
• Consequence: LINGO1 NM_032808.7 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.06

Genes affected

LINGO1 (HGNC:21205): (leucine rich repeat and Ig domain containing 1) Predicted to enable epidermal growth factor receptor binding activity. Predicted to act upstream of or within generation of neurons and protein kinase B signaling. Predicted to be located in plasma membrane. Predicted to be active in extracellular matrix and extracellular space. Implicated in autosomal recessive non-syndromic intellectual disability and glaucoma. [provided by Alliance of Genome Resources, Apr 2022]

LOC105370906 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.58).
• BP6: Variant 15-77614077-G-A is Benign according to our data. Variant chr15-77614077-G-A is described in ClinVar as [Benign]. Clinvar id is 779902.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-1.07 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00798 (1215/152304) while in subpopulation AFR AF= 0.0268 (1114/41564). AF 95% confidence interval is 0.0255. There are 18 homozygotes in gnomad4. There are 586 alleles in male gnomad4 subpopulation. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 18 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LINGO1	NM_032808.7	c.1830C>T	p.Asp610=	synonymous_variant	2/2	ENST00000355300.7
LOC105370906	XR_001751806.2	n.689-16208G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LINGO1	ENST00000355300.7	c.1830C>T	p.Asp610=	synonymous_variant	2/2	1	NM_032808.7	A1
LINGO1	ENST00000561030.5	c.1812C>T	p.Asp604=	synonymous_variant	4/4	1		P4

Frequencies

GnomAD3 genomes AF: 0.00798 AC: 1214 AN: 152186 Hom.: 18 Cov.: 33

Gnomad AFR AF: 0.0269

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00451

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000294

Gnomad OTH AF: 0.00574

GnomAD3 exomes AF: 0.00218 AC: 522 AN: 239226 Hom.: 7 AF XY: 0.00180 AC XY: 234 AN XY: 130322

Gnomad AFR exome AF: 0.0295

Gnomad AMR exome AF: 0.00161

Gnomad ASJ exome AF: 0.000203

Gnomad EAS exome AF: 0.0000579

Gnomad SAS exome AF: 0.000166

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000234

Gnomad OTH exome AF: 0.000852

GnomAD4 exome AF: 0.000942 AC: 1373 AN: 1457956 Hom.: 20 Cov.: 31 AF XY: 0.000862 AC XY: 625 AN XY: 724986

Gnomad4 AFR exome AF: 0.0277

Gnomad4 AMR exome AF: 0.00176

Gnomad4 ASJ exome AF: 0.000307

Gnomad4 EAS exome AF: 0.0000253

Gnomad4 SAS exome AF: 0.0000699

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000186

Gnomad4 OTH exome AF: 0.00227

GnomAD4 genome AF: 0.00798 AC: 1215 AN: 152304 Hom.: 18 Cov.: 33 AF XY: 0.00787 AC XY: 586 AN XY: 74462

Gnomad4 AFR AF: 0.0268

Gnomad4 AMR AF: 0.00451

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000294

Gnomad4 OTH AF: 0.00568

Alfa AF: 0.00536 Hom.: 4

Bravo AF: 0.00948

Asia WGS AF: 0.00115 AC: 4 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Dec 31, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.58
Cadd	Benign	5.1
Dann	Benign	0.81

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs113716376; hg19: chr15-77906419;